Abstract Eye diseases of young children, if not detected and treated early, can lead to serious vision loss and even blindness. Currently, retinal diseases in young children are mainly recorded and monitored by color photographs, even though they provide limited information about ophthalmic disease processes and mechanisms. As an alternative to the classic 2-D color photographs, novel spectral domain optical coherence tomography (SDOCT) imaging systems can provide 3-D images of intra-retinal structures. In adults, tabletop SDOCT provides significantly more useful diagnostic information and is now a standard for the diagnosis and management of retinal diseases. Our preliminary studies based on handheld SDOCT (HH-SDOCT) snapshots of neonatal retina have already provided some unique and previously unseen information about disease progression in young children. However, due to the infant's head/eye motion, it is extremely cumbersome to effectively image a complete 3-D tomographic view of the macula in young, awake children and accurately measure and quantify disease biomarkers. Our long-term goal is to improve the vision outcomes of at-risk young children with ocular diseases through earlier and better-directed therapy. To achieve this goal, we will take advantage of recent advances in image processing and optics as an integrated technology to capture 3-D retinal images with higher resolution and better motion stability compared to any previous imaging technique, which will ultimately provide quantitative measurements of novel imaging biomarkers of the onset and progression of young children's ophthalmic diseases. We will achieve our objectives by pursuit of the following three specific aims: Aim 1: Develop hardware to customize the handheld SDOCT and Doppler-SDOCT systems for retinal imaging of non- sedated young children. Aim 2: Develop software to control the hardware in Aim 1 and to automatically analyze the captured images for detecting imaging biomarkers of the onset and progression of retinal diseases in young children. Aim 3: Perform a pilot study in adults and young children. Evaluate, provide feedback, and improve the performance of methodologies in Aims 1&2, and then test the utility and validity of images and measurements compared to conventional diagnostic methods. The results of this study have the potential to provide practical diagnostic tools and methodologies that will revolutionize the management of pediatric ocular diseases. This contribution would be significant as the first step in a continuum of research leading to better-directed therapy of ocular diseases in young children based on accurate quantitative measurement of disease imaging biomarkers and accurate staging of foveal development.